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Genistein exhibits anti-cancer effects via down-regulating FoxM1 in H446 small-cell lung cancer cells

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Tumor Biology

Abstract

Genistein, a major isoflavone constituent in soybeans, has been reported to exhibit multiple anti-tumor effects, such as inducing cell cycle arrest, triggering apoptosis, and inactivating critical signaling pathways in a few human cancer cells. Here, we investigated the anti-tumor effects of genistein on the small-cell lung cancer (SCLC) cell line H446 and the underlying molecular mechanisms. H446 cells were treated with various concentrations of genistein, and experiments including CCK-8 assay, colony formation assay, flow cytometry analysis, wound healing assay, real-time polymerase chain reaction (PCR), western blot analysis, and plasmid transfection were used to investigate the influence of genistein on cell proliferation, migration ability, apoptosis, cell cycle progression, as well as the mRNA and protein alterations of FoxM1 pathway molecules. We found that genistein significantly inhibited the proliferation and migration ability of H446 cell, accompanied by apoptosis and G2/M phase cell cycle arrest. In addition, genistein enhanced the anti-proliferative effect of cisplatin on H446 cells. Importantly, genistein led to attenuation of the FoxM1 protein and down-regulated a series of FoxM1 target genes regulating cell cycle and apoptosis including Cdc25B, cyclin B1, and survivin. In addition, up-regulation of FoxM1 by cDNA transfection prior to genistein treatment could reduce genistein-induced H446 proliferation inhibition. Thus, for the first time, we demonstrated that genistein exerted multiple anti-tumor effects in H446 SCLC cell line at least partly mediated by the down-regulation of FoxM1. FoxM1 has the potential as a novel therapeutic agent in SCLC and is worthy of further study.

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Acknowledgments

This study was funded by the Science and Technology Development Projects of Shandong Province of China (2012GSF11845), Science and Technology Development Projects of Jinan City of Shandong Province (JN100503), Independent Innovation Foundation of Shandong University (2012TS155), and National Natural Science Foundation of China (81372530, 81201934).

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Authors and Affiliations

  1. Department of Medical Oncology, Cancer center, Qilu Hospital of Shandong University, Jinan, 250012, China

    Tiantian Tian, Jisheng Li, Bei Li, Yawei Wang, Meiying Li & Xiuwen Wang

  2. Department of Hematology, Cancer Center, Qilu Hospital of Shandong University, Jinan, 250012, China

    Daoxin Ma

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  1. Tiantian Tian
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  2. Jisheng Li
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Correspondence to Xiuwen Wang.

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Tiantian Tian and Jisheng Li contributed equally to this work.

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Tian, T., Li, J., Li, B. et al. Genistein exhibits anti-cancer effects via down-regulating FoxM1 in H446 small-cell lung cancer cells. Tumor Biol. 35, 4137–4145 (2014). https://doi.org/10.1007/s13277-013-1542-0

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  • DOI: https://doi.org/10.1007/s13277-013-1542-0

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